LILRB4 (leukocyte immunoglobulin like receptor B4)

Gene

• Entrez ID: 11006
• Gene name: Leukocyte immunoglobulin like receptor B4
• Gene symbol: LILRB4
• Synonyms (NCBI Gene): B4, CD85K, ILT-3, ILT3, LIR-5, LIR5
• Chromosome: 19
• Chromosome location: 19q13.42
• Summary: This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017863	hsa-miR-335-5p	Microarray	18185580
MIRT052507	hsa-let-7a-5p	CLASH	23622248
MIRT1109366	hsa-miR-1243	CLIP-seq
MIRT1109367	hsa-miR-129-5p	CLIP-seq
MIRT1109368	hsa-miR-1827	CLIP-seq
MIRT1109369	hsa-miR-2115	CLIP-seq
MIRT1109370	hsa-miR-2355-3p	CLIP-seq
MIRT1109371	hsa-miR-2964a-5p	CLIP-seq
MIRT1109372	hsa-miR-3612	CLIP-seq
MIRT1109373	hsa-miR-3618	CLIP-seq
MIRT1109374	hsa-miR-3654	CLIP-seq
MIRT1109375	hsa-miR-4443	CLIP-seq
MIRT1109376	hsa-miR-4477a	CLIP-seq
MIRT1109377	hsa-miR-4646-3p	CLIP-seq
MIRT1109378	hsa-miR-4684-5p	CLIP-seq
MIRT1109379	hsa-miR-4768-5p	CLIP-seq
MIRT1109380	hsa-miR-4775	CLIP-seq
MIRT1109381	hsa-miR-590-3p	CLIP-seq
MIRT1109382	hsa-miR-650	CLIP-seq
MIRT1109383	hsa-miR-934	CLIP-seq
MIRT1109366	hsa-miR-1243	CLIP-seq
MIRT1109368	hsa-miR-1827	CLIP-seq
MIRT1109371	hsa-miR-2964a-5p	CLIP-seq
MIRT1109372	hsa-miR-3612	CLIP-seq
MIRT1109373	hsa-miR-3618	CLIP-seq
MIRT1109374	hsa-miR-3654	CLIP-seq
MIRT2465551	hsa-miR-4276	CLIP-seq
MIRT1109375	hsa-miR-4443	CLIP-seq
MIRT1109382	hsa-miR-650	CLIP-seq
MIRT1109383	hsa-miR-934	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
TRERF1	Repression	18652845

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001968	Function	Fibronectin binding	IDA	34089617
GO:0002250	Process	Adaptive immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002507	Process	Tolerance induction	IDA	18420485, 20935202
GO:0002669	Process	Positive regulation of T cell anergy	IMP	16493035
GO:0002725	Process	Negative regulation of T cell cytokine production	IDA	18420485
GO:0002764	Process	Immune response-regulating signaling pathway	IBA
GO:0002774	Process	Fc receptor mediated inhibitory signaling pathway	IDA	16493035, 18420485
GO:0005515	Function	Protein binding	IPI	18802077
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	NAS	9548455
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	TAS	9151699
GO:0009986	Component	Cell surface	IDA	9151699, 19833736
GO:0016020	Component	Membrane	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA
GO:0019903	Function	Protein phosphatase binding	IPI	16493035
GO:0030292	Function	Protein tyrosine kinase inhibitor activity	IMP	16493035
GO:0030293	Function	Transmembrane receptor protein tyrosine kinase inhibitor activity	IDA	9151699
GO:0030547	Function	Signaling receptor inhibitor activity	IDA	9151699
GO:0031623	Process	Receptor internalization	IMP	9151699
GO:0032396	Function	Inhibitory MHC class I receptor activity	IBA
GO:0032682	Process	Negative regulation of chemokine production	IMP	19380766
GO:0032689	Process	Negative regulation of type II interferon production	IDA	20007427
GO:0032691	Process	Negative regulation of interleukin-1 beta production	IMP	19380766
GO:0032693	Process	Negative regulation of interleukin-10 production	IDA	18420485
GO:0032703	Process	Negative regulation of interleukin-2 production	IDA	18420485
GO:0032714	Process	Negative regulation of interleukin-5 production	IDA	18420485
GO:0032715	Process	Negative regulation of interleukin-6 production	IMP	19380766
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IDA	19833736
GO:0034185	Function	Apolipoprotein binding	IDA	30333625
GO:0042130	Process	Negative regulation of T cell proliferation	IMP	17163451
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	IMP	19380766
GO:0043378	Process	Positive regulation of CD8-positive, alpha-beta T cell differentiation	IDA	18420485
GO:0043409	Process	Negative regulation of MAPK cascade	IMP	19380766
GO:0045584	Process	Negative regulation of cytotoxic T cell differentiation	IMP	16493035
GO:0045591	Process	Positive regulation of regulatory T cell differentiation	IDA	20935202, 22387553
GO:0045671	Process	Negative regulation of osteoclast differentiation	IDA	18802077
GO:0046007	Process	Negative regulation of activated T cell proliferation	IMP	19380766
GO:0050860	Process	Negative regulation of T cell receptor signaling pathway	IDA	22387553
GO:0050860	Process	Negative regulation of T cell receptor signaling pathway	IMP	16493035
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0071659	Process	Negative regulation of IP-10 production	IMP	19380766
GO:0140105	Process	Interleukin-10-mediated signaling pathway	IEP	17163451
GO:0150102	Process	Negative regulation of monocyte activation	IDA	19833736, 34089617
GO:0150102	Process	Negative regulation of monocyte activation	IMP	9151699
GO:1900016	Process	Negative regulation of cytokine production involved in inflammatory response	IMP	19380766
GO:1900181	Process	Negative regulation of protein localization to nucleus	IDA	22387553
GO:1902532	Process	Negative regulation of intracellular signal transduction	IDA	9151699
GO:1902894	Process	Negative regulation of miRNA transcription	IDA	22387553
GO:2000524	Process	Negative regulation of T cell costimulation	IMP	17163451

Other IDs

• MIM: 604821
• HGNC: 6608
• e!Ensembl: ENSG00000186818

Protein

• UniProt ID: Q8NHJ6
• Protein name: Leukocyte immunoglobulin-like receptor subfamily B member 4 (B4) (CD85 antigen-like family member K) (Immunoglobulin-like transcript 3) (ILT-3) (Leukocyte immunoglobulin-like receptor 5) (LIR-5) (Monocyte inhibitory receptor HM18) (CD antigen CD85k)
• Protein function: Inhibitory receptor involved in the down-regulation of the immune response and the development of immune tolerance (PubMed:11875462). Receptor for FN1 (PubMed:34089617). Receptor for apolipoprotein APOE (PubMed:30333625). Receptor for ALCAM/CD16
• PDB: 3P2T, 6K7O
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13895	Ig_2	28 → 117	Immunoglobulin domain	Domain
  PF00047	ig	127 → 209	Immunoglobulin domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected on monocytes, macrophages, dendritic cells, natural killer cells and B-cells (at protein level). Expressed in the lung. {ECO:0000269|PubMed:19833736, ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:9151699, ECO:0000269|PubMed:
• Sequence:

  MIPTFTALLCLGLSLGPRTHMQAGPLPKPTLWAEPGSVISWGNSVTIWCQGTLEAREYRL
  DKEESPAPWDRQNPLEPKNKARFSIPSMTEDYAGRYRCYYRSPVGWSQPSDPLELVMTGA
  YSKPTLSALPSPLVTSGKSVTLLCQSRSPMDTFLLIKERAAHPLLHLRSEHGAQQHQAEF
  PMSPVTSVHGGTYRCFSSHGFSHYLLSHPSDPLELIVSGSLEDPRPSPTRSVSTAAGPED
  QPLMPTGSVPHSGLRRHWEVLIGVLVVSILLLSLLLFLLLQHWRQGKHRTLAQRQADFQR
  PPGAAEPEPKDGGLQRRSSPAADVQGENFCAAVKNTQPEDGVEMDTRQSPHDEDPQAVTY
  AKVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTEAAASEAPQDVTYAQLHSFTL
  RQKATEPPPSQEGASPAEPSVYATLAIH

• Sequence length: 448

Pathways

KEGG:

Osteoclast differentiation
B cell receptor signaling pathway

Reactome:

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute monocytic leukemia	Monocytic Leukemia	BEFREE	30131301		★☆☆☆☆ Found in Text Mining only
Acute myelomonocytic leukemia	Myelomonocytic Leukemia	BEFREE	23027709		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	40702763	Associate	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	28743735		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	10940079		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	28743735		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	17513794, 17923119, 23018130, 29951069, 30126665		★☆☆☆☆ Found in Text Mining only
B-CELL MALIGNANCY, LOW-GRADE	Lymphocytic Leukemia	BEFREE	28931525		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	35321724	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	36748687	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	17266150, 28931525		★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	24347371	Stimulate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30126665		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34054869	Associate	★☆☆☆☆ Found in Text Mining only
Common Variable Immunodeficiency	Common variable immunodeficiency	Pubtator	33190167	Associate	★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	23027709		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	30581005		★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Demyelinating diseases	Pubtator	25551576	Associate	★☆☆☆☆ Found in Text Mining only
Graft-vs-Host Disease	Graft-Vs-Host Disease	BEFREE	19501624		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	30581005		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	20398663		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	40516328	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	23027709, 32036728, 34712735, 40516328	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myelomonocytic Chronic	Myelomonocytic leukemia	Pubtator	32036728	Stimulate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	23027709, 30131301, 30333625, 31213474, 31700117		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus	Lupus Erythematosus	BEFREE	22904259		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	22904259	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Discoid	Lupus Erythematosus	BEFREE	22904259		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	22904259, 30768140		★☆☆☆☆ Found in Text Mining only
Lupus Vulgaris	Lupus Vulgaris	BEFREE	22904259		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	22246571		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	17513794, 17923119, 19860908, 28931525, 29263213		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	29091299		★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	BEFREE	30882741		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	26545722, 37276129	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	25551576		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	25551576	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17513794, 22246571, 29263213, 30126665, 30333625		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	40702763	Associate	★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	29091299		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasm	Pancreatic Neoplasm	LHGDN	17993722		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	40702763	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	22246571		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	22246571	Associate	★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	24347371		★☆☆☆☆ Found in Text Mining only